SLiM-binding pockets: an attractive target for broad-spectrum antivirals

Area of Science:

• Molecular biology
• Virology
• Drug discovery

Background:

• Short linear motifs (SLiMs) mediate critical protein-protein interactions.
• Viruses extensively mimic host SLiMs to manipulate cellular functions.
• Conserved SLiM-binding pockets are frequently targeted by multiple unrelated viruses.

Purpose of the Study:

• To highlight the therapeutic potential of SLiMs as targets for antiviral intervention.
• To advocate for the development of therapeutics targeting commonly mimicked SLiMs.

Main Methods:

• This opinion article reviews existing literature on SLiM biology and viral mimicry.
• It analyzes the implications of SLiM-host interactions for antiviral drug development.

Main Results:

• SLiMs present compact, functionally important interfaces for viral manipulation.
• The convergent evolution of SLiM mimicry by viruses creates vulnerabilities.
• Commonly targeted SLiM-binding pockets represent attractive targets for broad-spectrum antivirals.

Conclusions:

• Targeting SLiMs is a viable strategy for developing broad-spectrum antiviral agents.
• A toolkit of SLiM-based inhibitors could enhance preparedness for viral outbreaks.
• SLiMs are highly suitable targets for novel antiviral therapies.